This study aimed to determine the effects of whey protein supplementation (WPS) and exercise on body composition, lipid, glucose and renal function among overweight and obese individuals. A parallel-design comparison study was conducted among 80 overweight or obese adults. Subjects with similar characteristics were matched and randomly assigned to 1 of the 4 groups: control, exercise, WPS or WPS plus exercise group for 12 weeks. Two groups (1. WPS group and 2. WPS + exercise group) consumed 29g whey protein mixed in 300mL water 30 minutes before breakfast and dinner twice daily. The two groups which included exercise (1. exercise group and 2. WPS + exercise group) increased exercise 30 minutes daily, 5 days weekly. Body composition, lipids, glucose, and renal function were assessed at weeks 0, 6 and 12. Between-group mean changes in parameters after six and 12 weeks were assessed using one-way ANOVA. Time points were compared within groups using one-way repeated measures ANOVA and Duncan post hoc comparison. 62 subjects completed the study. The WPS + exercise group exhibited significantly improved body composition, blood glucose and total cholesterol at 12 weeks compared with baseline (p < 0.05). Triglyceride, LDL cholesterol, HDL cholesterol, blood urea nitrogen, creatinine, and uric acid did not significantly differ in all groups. Supplementation using whey protein and exercise may improve body composition, plasma glucose and total cholesterol among overweight and obese adults. However, a decrease in dietary intake was observed in the intervention group that could have changed body composition. Consequently, the relationship between supplementation, exercise, dietary intake and body composition needs to be clarified in a future study.